ASPIRIN-INDUCED GASTRITIS, LIKE HELICOBACTER PYLORI-INDUCED GASTRITIS, DISINHIBITS ACID-SECRETION IN HUMANS - RELATION TO CYTOKINE EXPRESSION

Background: Helicobacter pylori infection contributes to hypergastrine mia and hypersecretion of acid by blocking inhibitory reflex pathways to gastrin and parietal cells normally activated by antral distention. Our aim was to investigate whether a similar blockade of inhibitory r esponses could be provoked by inducing gastritis with aspirin, thus im plicating a common inflammatory component, possibly a proinflammatory cytokine(s). Methods: We studied the effects of antral distention on s timulated acid secretion and gastrin release in H. pylori-negative vol unteers, before and after 3 days of aspirin therapy (2 g daily). Immed iately before the examinations, they severity of gastric mucosal injur y was evaluated macroscopically and histologically, and the production of interleukin (IL)-1 beta, IL-6, IL-8, tumor necrosis factor (TNF)-a lpha, and interferon (IFN)-gamma was determined by immunohistochemistr y. Results: Most subjects had severe gastric injury after aspirin ther apy, resulting in a substantially increased production of IL-1 beta, I L-6, and IL-8 but not of TNF-alpha and IFN-gamma in the antral mucosa. In these subjects the acid-inhibitory response was abolished or marke dly reduced. Conversely, aspirin therapy failed to affect the gastrin release in all subjects studied. Conclusions: The disinhibition of aci d secretion in response to antral distention is a joint feature of the gastritis induced by aspirin and H. pylori infection, possibly relate d to the increased production of IL-1 beta, IL-6, and IL-8. The H. pyl ori-related hypergastrinemia apparently has a different background.